ArticleNucleic acids research2020
The SINEB1 element in the long non-coding RNA Malat1 is necessary for TDP-43 proteostasis.
Article in Nucleic acids research, 2020. The graph could read no effect estimate from its abstract, so it casts no vote on the map. Cited by 47 papers.
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Who cites it
47 citing papers in PubMed, 63 citations in OpenAlex.
- A B1 SINE element within the mouseScience advances · 2026Article
- Scanning transcriptomes for nonlinear, domain-level similarities using hmSEEKR.bioRxiv : the preprint server for biology · 2026Article
- Interaction between lncRNAs and RNA binding proteins, and their potential as drug targets in the therapy of liver cancer (Review).Biomedical reports · 2026Review
- RNA-binding protein hnRNPK: a multifunctional regulator of skeletal muscle biology and disease.Biochemical Society transactions · 2026Review
- Uncertainty-aware benchmarking reveals ambiguous transcripts in mRNA-lncRNA classification.bioRxiv : the preprint server for biology · 2026Article
- Prion propagation is controlled by a hierarchical network involving the nuclear Tfap2c and hnRNP K factors and the cytosolic mTORC1 complex.PLoS pathogens · 2026Article
- MicroRNAs and Long Non-Coding RNAs Affect the Mechanisms Involved in Age-Related Neurodegeneration in a Manner Depending on RNA-Binding Proteins.Molecular neurobiology · 2026Review
- Histone modification-regulated LncRNA DLEU1 interacts with ASCC2/ALKBH3 complex to drive DNA repair, antioxidant homeostasis and glucose metabolism in gastric cancer.Biomarker research · 2026Article
- RNA methylation modifications in neurodegenerative diseases: Focus on their enzyme system.Journal of advanced research · 2025Review
- TDP-43: unveiling the hidden key to cellular fate decisions.Cell communication and signaling : CCS · 2025Review
- Regulation of the lncRNANAR molecular medicine · 2025Article
- Inclusion body myositis, viral infections, and TDP-43: a narrative review.Clinical and experimental medicine · 2024Review
- Expression Pattern and Prognostic Significance of the Long Non-Coding RNA Metastasis-Associated Lung Adenocarcinoma Transcript 1 in Chronic Lymphocytic Leukemia.International journal of molecular sciences · 2024Article
- Fear extinction is regulated by the activity of long noncoding RNAs at the synapse.Nature communications · 2023Article
- lhCLIP reveals the in vivo RNA-RNA interactions recognized by hnRNPK.PLoS genetics · 2023Article
- Exosomes-transferred LINC00668 Contributes to Thrombosis by Promoting NETs Formation in Inflammatory Bowel Disease.Advanced science (Weinheim, Baden-Wurttemberg, Germany) · 2023Article
- High Throughput FISH Screening Identifies Small Molecules That Modulate Oncogenic lncRNA MALAT1 via GSK3B and hnRNPs.Non-coding RNA · 2023Article
- RNA binding proteins (RBPs) and their role in DNA damage and radiation response in cancer.Advanced drug delivery reviews · 2022Review
- Altered TDP-43 Structure and Function: Key Insights into Aberrant RNA, Mitochondrial, and Cellular and Systemic Metabolism in Amyotrophic Lateral Sclerosis.Metabolites · 2022Review
- Nuclear RNA binding regulates TDP-43 nuclear localization and passive nuclear export.Cell reports · 2022Article
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Authors and funding
24 authors at 6 institutions in 1 country.
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Abstract
Transposable elements (TEs) comprise a large proportion of long non-coding RNAs (lncRNAs). Here, we employed CRISPR to delete a short interspersed nuclear element (SINE) in Malat1, a cancer-associated lncRNA, to investigate its significance in cellular physiology. We show that Malat1 with a SINE deletion forms diffuse nuclear speckles and is frequently translocated to the cytoplasm. SINE-deleted cells exhibit an activated unfolded protein response and PKR and markedly increased DNA damage and apoptosis caused by dysregulation of TDP-43 localization and formation of cytotoxic inclusions. TDP-43 binds stronger to Malat1 without the SINE and is likely 'hijacked' by cytoplasmic Malat1 to the cytoplasm, resulting in the depletion of nuclear TDP-43 and redistribution of TDP-43 binding to repetitive element transcripts and mRNAs encoding mitotic and nuclear-cytoplasmic regulators. The SINE promotes Malat1 nuclear retention by facilitating Malat1 binding to HNRNPK, a protein that drives RNA nuclear retention, potentially through direct interactions of the SINE with KHDRBS1 and TRA2A, which bind to HNRNPK. Losing these RNA-protein interactions due to the SINE deletion likely creates more available TDP-43 binding sites on Malat1 and subsequent TDP-43 aggregation. These results highlight the significance of lncRNA TEs in TDP-43 proteostasis with potential implications in both cancer and neurodegenerative diseases.
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